Several lines of evidence indicate that the differentiation of the embryonal carcinoma, the stem cell of the teratoma, requires an interaction with the milieu created by normal cells. We have also found that an interaction occurs between teratocarcinoma cells and cerebellar cells in reaggregating cell cultures which results in an inhibition of accumulation of adult-type L-glycerol 3-phosphate dehydrogenase (alpha-GPDH). This observation suggests that the teratocarcinoma-cerebellar cell interaction may serve as a model system by which interactions at the cell surface lead to a modulation of specific gene expression. Our experimental approach to test the validity of the model system is to purify plasma membrane fractions from tumor cells known to block alpha-GPDH expression. The ligands and receptors involved in the interaction will be characterized by assessing the effects of treatments with proteases, nuclease and glycosidase. Plasma membrane fractions will also be labeled in vivo with radioactive substrates and in vitro by the lactoperoxidase catalyzed iodinations. This will allow us to establish dosage relationships between the amount of plasma membrane added to cultures and the degree of alpha-GPDH reduction. It will allow to begin further characterization of the ligands and receptors by polyacrylamide gell electrophoresis. Purification of ligands involved in the cell surface interaction will be undertaken with the view toward producing antibody against the ligands. The availability of antibody will allow us to localize the ligands and receptors and also to determine the range of cell types that possess such receptors.